Jennifer A. Nettleton

Diet Soda Intake and Risk of Incident Metabolic Syndrome and Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVE We determined associations between diet soda consumption and risk of incident metabolic syndrome, its components, and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis. RESEARCH DESIGN AND METHODS Diet soda consumption was assessed by food frequency questionnaire at baseline (2000–2002). Incident type 2 diabetes was identified at three follow-up examinations (2002–2003, 2004–2005, and 2005–2007) as fasting glucose >126 mg/dl, self-reported type 2 diabetes, or use of diabetes medication. Metabolic syndrome (and components) was defined by National Cholesterol Education Program Adult Treatment Panel III criteria. Hazard ratios (HRs) with 95% CI for type 2 diabetes, metabolic syndrome, and metabolic syndrome components were estimated, adjusting for demographic, lifestyle, and dietary confounders. RESULTS At least daily consumption of diet soda was associated with a 36% greater relative risk of incident metabolic syndrome and a 67% greater relative risk of incident type 2 diabetes compared with nonconsumption (HR 1.36 [95% CI 1.11–1.66] for metabolic syndrome and 1.67 [1.27–2.20] for type 2 diabetes). Of metabolic syndrome components, only high waist circumference (men ≥102 cm and women ≥88 cm) and high fasting glucose (≥100 mg/dl) were prospectively associated with diet soda consumption. Associations between diet soda consumption and type 2 diabetes were independent of baseline measures of adiposity or changes in these measures, whereas associations between diet soda and metabolic syndrome were not independent of these factors. CONCLUSIONS Although these observational data cannot establish causality, consumption of diet soda at least daily was associated with significantly greater risks of select incident metabolic syndrome components and type 2 diabetes.

Fast-Food Consumption, Diet Quality, and Neighborhood Exposure to Fast Food The Multi-Ethnic Study of Atherosclerosis

The authors examined associations among fast-food consumption, diet, and neighborhood fast-food exposure by using 2000-2002 Multi-Ethnic Study of Atherosclerosis data. US participants (n = 5,633; aged 45-84 years) reported usual fast-food consumption (never, <1 time/week, or > or =1 times/week) and consumption near home (yes/no). Healthy diet was defined as scoring in the top quintile of the Alternate Healthy Eating Index or bottom quintile of a Western-type dietary pattern. Neighborhood fast-food exposure was measured by densities of fast-food outlets, participant report, and informant report. Separate logistic regression models were used to examine associations of fast-food consumption and diet; fast-food exposure and consumption near home; and fast-food exposure and diet adjusted for site, age, sex, race/ethnicity, education, and income. Those never eating fast food had a 2-3-times higher odds of having a healthy diet versus those eating fast food > or =1 times/week, depending on the dietary measure. For every standard deviation increase in fast-food exposure, the odds of consuming fast food near home increased 11%-61% and the odds of a healthy diet decreased 3%-17%, depending on the model. Results show that fast-food consumption and neighborhood fast-food exposure are associated with poorer diet. Interventions that reduce exposure to fast food and/or promote individual behavior change may be helpful.

Availability of healthy foods and dietary patterns: the Multi-Ethnic Study of Atherosclerosis

BACKGROUND Inadequate availability of healthy foods may be a barrier to achieving recommended diets. OBJECTIVE The objective was to study the association between the directly measured availability of healthy foods and diet quality. DESIGN We conducted a cross-sectional study of 759 participants from the Baltimore site of the Multi-Ethnic Study of Atherosclerosis. Diet was characterized by using a food-frequency questionnaire and summarized by using 2 empirically derived dietary patterns reflecting low- and high-quality diets. For each participant, the availability of healthy foods was directly assessed by using 3 measures: in all food stores within their census tract, in their closest food store, and in all food stores within 1 mile (1.6 km) of their residence. RESULTS Twenty-four percent of the black participants lived in neighborhoods with a low availability of healthy food compared with 5% of white participants (P < 0.01). After adjustment for age, sex, income, and education, a lower availability of healthy foods in the tract of residence or in the closest store was associated with higher scores on the low-quality dietary pattern (P < 0.05). Less consistent associations were observed for the high-quality dietary pattern. CONCLUSIONS Healthy foods were less available for black participants. Low availability of healthy foods was associated with a lower-quality diet. The extent to which improvements in the availability of healthy foods results in higher-quality diets deserves further investigation.

Genetic loci associated with plasma phospholipid N-3 fatty acids: A Meta-Analysis of Genome-Wide association studies from the charge consortium

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis

BACKGROUND Although dietary recommendations have focused on restricting saturated fat (SF) consumption to reduce cardiovascular disease (CVD) risk, evidence from prospective studies has not supported a strong link between total SF intake and CVD events. An understanding of whether food sources of SF influence these relations may provide new insights. OBJECTIVE We investigated the association of SF consumption from different food sources and the incidence of CVD events in a multiethnic population. DESIGN Participants who were 45-84 y old at baseline (n = 5209) were followed from 2000 to 2010. Diet was assessed by using a 120-item food-frequency questionnaire. CVD incidence (316 cases) was assessed during follow-up visits. RESULTS After adjustment for demographics, lifestyle, and dietary confounders, a higher intake of dairy SF was associated with lower CVD risk [HR (95% CI) for +5 g/d and +5% of energy from dairy SF: 0.79 (0.68, 0.92) and 0.62 (0.47, 0.82), respectively]. In contrast, a higher intake of meat SF was associated with greater CVD risk [HR (95% CI) for +5 g/d and a +5% of energy from meat SF: 1.26 (1.02, 1.54) and 1.48 (0.98, 2.23), respectively]. The substitution of 2% of energy from meat SF with energy from dairy SF was associated with a 25% lower CVD risk [HR (95% CI): 0.75 (0.63, 0.91)]. No associations were observed between plant or butter SF and CVD risk, but ranges of intakes were narrow. CONCLUSION Associations of SF with health may depend on food-specific fatty acids or other nutrient constituents in foods that contain SF, in addition to SF.

Dietary patterns and risk of incident type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE—We characterized dietary patterns and their relation to incident type 2 diabetes in 5,011 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). RESEARCH DESIGN AND METHODS—White, black, Hispanic, and Chinese adults, aged 45–84 years and free of cardiovascular disease and diabetes, completed food frequency questionnaires at baseline (2000–2002). Incident type 2 diabetes was defined at three follow-up exams (2002–2003, 2004–2005, and 2005–2007) as fasting glucose >126 mg/dl, self-reported type 2 diabetes, or use of diabetes medication. Two types of dietary patterns were studied: four empirically derived (principal components analysis) and one author-defined (low-risk food pattern) as the weighted sum of whole grains, vegetables, nuts/seeds, low-fat dairy, coffee (positively weighted), red meat, processed meat, high-fat dairy, and soda (negatively weighted). RESULTS—The empirically derived dietary pattern characterized by high intake of tomatoes, beans, refined grains, high-fat dairy, and red meat was associated with an 18% greater risk (hazard ratio per 1-score SD 1.18 [95% CI 1.06–1.32]; Ptrend = 0.004), whereas the empirically derived dietary pattern characterized by high intake of whole grains, fruit, nuts/seeds, green leafy vegetables, and low-fat dairy was associated with a 15% lower diabetes risk (0.85 [0.76–0.95]; Ptrend = 0.005). The low-risk food pattern was also inversely associated with diabetes risk (0.87 [0.81–0.99]; Ptrend = 0.04). Individual component food groups were not independently associated with diabetes risk. Associations were not modified by sex or race/ethnicity. CONCLUSIONS—Multiple food groups collectively influence type 2 diabetes risk beyond that of the individual food groups themselves.

Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4×10−19), near AHR, and 15q24 (P = 5.2×10−14), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2.

trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND Dairy consumption is linked to a lower risk of type 2 diabetes, but constituents responsible for this relation are not established. Emerging evidence suggests that trans-palmitoleate (trans 16:1n-7), a fatty acid in dairy and also partially hydrogenated oils, may be associated with a more favorable metabolic profile and less incident diabetes. OBJECTIVE We investigated the association of trans-palmitoleate with metabolic risk and incident diabetes in a multiethnic US cohort. DESIGN Phospholipid fatty acids and metabolic risk factors were measured in 2000-2002 among 2617 adults in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of white, black, Hispanic, and Chinese Americans. In 2281 participants free of baseline diabetes, we also prospectively assessed the risk of new-onset diabetes (205 cases) from baseline to 2005-2007. RESULTS trans-Palmitoleate concentrations correlated positively with self-reported consumption of whole-fat dairy, butter, margarine, and baked desserts and with other circulating biomarkers of both dairy fat and partially hydrogenated oil consumption, which suggested mixed dietary sources. After multivariable adjustment, trans-palmitoleate concentrations were associated with higher LDL cholesterol (quintile 5 compared with quintile 1: +6.4%; P-trend = 0.005), lower triglycerides (-19.1%; P-trend < 0.001), lower fasting insulin (-9.1%; P-trend = 0.002), and lower systolic blood pressure (-2.4 mm Hg; P-trend = 0.01). In prospective analyses, trans-palmitoleate was independently associated with lower incident diabetes (P-trend = 0.02), including a 48% lower risk in quintile 5 compared with quintile 1 (HR: 0.52; 95% CI: 0.32, 0.85). All findings were similar between men and women and between different race-ethnic subgroups. CONCLUSIONS Circulating trans-palmitoleate is associated with higher LDL cholesterol but also with lower triglycerides, fasting insulin, blood pressure, and incident diabetes in a multiethnic US cohort. Our findings support the need for further experimental and dietary intervention studies that target circulating trans-palmitoleate. The MESA trial was registered at clinicaltrials.gov as NCT00005487.

Dietary flavonoid intake and risk of cancer in postmenopausal women: The Iowa Women's Health Study

Flavonoids, which are found in certain plant foods, are thought to lower cancer risk through their antioxidant, antiestrogenic and antiproliferative properties. We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung, colorectal, breast, pancreatic and upper aerodigestive cancer among women in a large prospective cohort study. Study participants were 34,708 postmenopausal women in the Iowa Womens Health Study who completed a food frequency questionnaire and were followed for cancer occurrence from 1986 through 2004. Flavonoid intake was estimated from 3 databases developed by the USDA Nutrient Data Laboratory (NDL). Hazard ratios (HR) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories. Interactions between smoking history and flavonoid intake were also examined. After multivariable adjustment, lung cancer incidence was inversely associated with intakes of flavanones (HR = 0.68; 95% CI: 0.53–0.86, all results highest vs. lowest quintile) and proanthocyanidins (HR = 0.75; 95% CI: 0.57–0.97). Among current and past smokers, those with intakes in the highest quintile for flavanones (HR = 0.66; 95% CI: 0.50–0.86), and proanthocyanidins (HR = 0.66; 95% CI; 0.49–0.89) had significantly lower lung cancer incidence than those in the lowest quintile. Similar associations were not seen in never smokers. Isoflavone intake was inversely associated with overall cancer incidence (HR = 0.93, 95% CI: 0.86–1.00). This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk, especially among current and past smokers.

Interactions of dietary whole grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies

OBJECTIVE Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS Via meta-analysis of data from 14 cohorts comprising ∼48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. RESULTS Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: −0.009 mmol/l glucose [−0.013 to −0.005], P < 0.0001 and −0.011 pmol/l [ln] insulin [−0.015 to −0.007], P = 0.0003). No interactions met our multiple testing–adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.